Treatment Delay and Total Delay among Pulmonary Tuberculosis Patients in the North of Iran: Application Survival Data Analysis.

BACKGROUND
Tuberculosis (TB) remains the leading cause of death among infectious diseases worldwide. Identifying the factors associated with the treatment delay and total delay would be helpful in the prevention of tuberculosis and in reducing the burden on the health care system. The objective of this study was to assess the treatment delay and total delay in TB patients and investigate the factors causing these delays.


MATERIALS AND METHODS
This was a longitudinal study conducted in 2009-2015. Our study consisted of 1694 TB patients registered in the TB center of Mazandaran province. Data regarding the patients' demographic characteristics and clinical factors associated with treatment delay and total delay were analyzed. Kaplan Meier plots and log rank tests were used to assess the survival pattern. Cox proportional hazards model for multivariable analysis was discussed. We used mean values and median (Q2) [first quartile (Q1)-third quartile (Q3)] to describe delays.


RESULTS
The median treatment delay and total delay were 35 (ranged 23-80) and 36 (ranged 24-82) days, respectively. The mean age of TB patients was 47.40±20.3. No significant association was found between the location of residence, nationality, gender, and type of pulmonary TB patients with treatment delay and total delay. Additionally, age, prison status of patients, HIV test, and contact history had a significant relationship with the treatment delay and total delay (p-value <0.05). It was shown that the median total delay in men patients in the ≤14 year-old age group, imprisoner patients, rural patients, patients who have not received an HIV test, smear negative patients, those who are Iranian, and TB patients whose contact history was unknown was lower than that of others. The highest median treatment delay and total delay was in the >60 age groups, and were 41 and 44 days, respectively. Treatment delay was the same as the total delay except in the place of residence variable; median treatment delay among urban patients was less than that of rural patients.


CONCLUSION
According to this study age, prison status of patients, HIV test and contact history had a significant relationship with the treatment delay and total delay (P-value<0.05). Understanding the factors that are closely associated with these delays is essential to effectively control TB and could be helpful in reducing these delays.


INTRODUCTION
Despite the existence of effective treatment methods, tuberculosis (TB) remains one of the major infectious diseases prevalent in most countries (1)(2)(3). Based on a WHO report, there were an estimated 10.4 million incident TB cases worldwide, of which 5.9 million (56%) were among men, 3.5 million (34%) among women and 1.0 million (10%) among children (4). The incidence rate in Iran was reported as 12.6 per 100,000 population, and this rate is the highest in Sistan-Baluchistan and Golestan provinces (5,6).
A national survey conducted in Iran in 2003 showed that the median delay in diagnosis and treatment in patients with sputum positive pulmonary tuberculosis was 92 days (with an average of 120+10 days) and the median patient delay and median physicians delay in diagnosis was 20 (with an average of 44+6 days) and 46 days (with an average of 76+8 days), respectively (7). Transmission of TB is difficult to control, and one index case may infect a large number of secondary cases if left untreated (8-10); therefore, reducing the time delay from symptom onset initiation of treatment is required for better management of TB (9,11). The delay in treatment could be due to the delay in diagnosis by the physicians or due to the failure of the treatment provided, and due to these reasons, treatment delay may increase (12). Delay in accessing TB care is common in both industrialized and developing countries.
However, there is no international consensus on what constitutes an acceptable delay (13). The average delay in low-income countries has been reported to be 9.7 weeks (14). Since delays may increase mortality, the factors affecting treatment delay are of key importance in TB management (14,15). Since these delays may have adverse effects on the wellbeing of the society and the health system by possibly increasing the treatment duration, the aim of this study was to evaluate the survival of these patients and determine the factors that cause treatment delays in Mazandaran. Our study results would be useful for the health authorities and strategic planners in the design and implementation of interventional TB control programs, and in finding ways to treat and diagnose patients as early as possible.

Data analysis
We assessed the demographic characteristics affecting the treatment delay and total delay in patients, using Cox   A systematic review that investigated delays in diagnosis and treatment of pulmonary tuberculosis in India revealed that the median treatment delay was 2.5 days (1.9-3.6) which was shorter than the treatment delay found in our study (17). Other studies have also found shorter median for treatment delay, such as those in Guinea-Bissau (12.1 weeks) (18), in Tanzania (28 days) (19), in Botswana (5 weeks) (20), in Ethiopia (2 days) (21), and in Nigeria (11 weeks) (22). In a study conducted in Nigeria, it was found that the median treatment delay was one week and the median total delay was 10 weeks, which were longer than the delays found in our study (23).
Another study (24)  Information on better case detection should be included in trainings to familiarize the personnel and medical staff with the signs and symptoms of TB; equipping the laboratories appropriately will also enable them to diagnose TB cases better and efficiently (17).
In a study by Lienhardt et al., a total of 152 TB patients were interviewed. The median delay from the onset of symptoms to commencement of treatment was 8.6 weeks (range 5-17). Treatment delay was independent of gender, but was shorter in young TB patients. The median delay was longer in the rural areas than that in urban areas (28).
In our study, it was found that total delay was less than the abovementioned study and women had longer treatment delay than men, which may be because many women  (38).

CONCLUSION
The estimated median treatment delay and total delay were 35 and 36 days, respectively. We also found in our study that variables such as age, prison status, HIV testing, and patients who their contact history were unknown, had a significant relationship with the treatment delay and total delay (p-value<0.05).
Considering that the delay in TB treatment in our study was high and that TB is a contagious disease, it is recommended that diagnostic methods for TB should be emphasized in the training courses for medical students, continuing education courses for general physicians and specialists, and in post-graduate courses. To reduce the treatment delay, clinics need to be more involved and the referral mechanism must be strengthened. We also need to improve awareness of the symptoms of tuberculosis both in the general public and among health care professionals.
There has not been any studies regarding the delays among pulmonary tuberculosis patients in Mazandaran province and this study reports the situation regarding the delays among pulmonary tuberculosis patients in Mazandaran province, and provides recommendations for improvements to help with the planning to reduce these delays, and hence reduce the period of treatment. One of the limitations of our study was that the registry data had recording errors. Additionally, it is possible that not all of the patients in this province had been registered. We also noted that the information on social and economic variables was not complete and these variables could have an effect on treatment delay and total delay.